Encephalopathy: A Vicious Cascade Following Forebrain Ischemia and Hypoxia

Author(s):
Baowan Lin
Pages 57-70 (14)

Abstract:

Post ischemic/hypoxic encephalopathy is a progressive and widespread damage syndrome in human brain,
which includes production of new ischemic foci as well as neurodegeneration associated with accumulation of amyloid
protein (Aβ), which emerges within days after the primary ischemic or hypoxic ictus. Patients may suddenly suffer severe
dementia and Parkinson’s syndrome after a symptom-free period averaging 2 weeks following resuscitation. Death of
neurons in the cortex, limbic system, globus pallidus (GP) and substantia nigra (SN) and damage to white matter are
responsible. From experimental studies in animals evidence is obtained to reveal the mechanisms. Injured endothelia and
activated platelets lead to secondary injury via thrombosis and vasoconstriction resulting in infarction and new foci of
necrosis. Blood-brain barrier (BBB) breakdown allows penetration of blood-borne toxic substances into brain resulting in
neuronal degeneration and enhanced inflammatory destruction. These secondary injuries happen within two weeks after
moderate global ischemia. As these pathological changes cycle between the vascular and neuronal compartments, the
damage expands and worsens. Aβ, β amyloid precursor protein (βAPP) and the inflammation mediator cyclooxygenase-2
(COX2) as well as γ-aminobutyric acid (GABA) system degeneration participate in producing secondary injury. Thus,
implementing multi-targeted prophylaxis before or at the brain-at-risk stage is desirable. A combination of protecting
endothelia, inhibiting platelet activity and improving cerebral circulation is a fundamental strategy to block this vicious
cascade, thereby ameliorating or preventing the encephalopathy.